1. Field of the Invention
This invention relates to the controlled release of medications or active substances which are administered transdermally. More particularly, this invention relates to matrices which are solids, at ambient temperatures and body temperatures, which are useful for controlling the release of at least one drug or medication. The matrices have a relatively low glass transition temperature such that various drugs can be incorporated, without heat damage, by melting or softening the matrix composition and mixing the drug into the softened composition.
2. Description of the Prior Art
Matrices have hithertofore been used as a drug reservoir component of transdermal drug delivery devices. Often gels or pastes of various compositions have been employed in such applications because of the difficulty of incorporating drugs into resinous or elastomeric materials and also because many elastomers lack the desired permeability to various drugs and medications. Such matrices in the past have often lacked sufficient cohesive strength to be used alone and thus they had to be covered by membranes designed to control the rate at which the medications are released into the skin of the patient. Generally an impermeable backing material covers the top of the composite structure, and a pressure sensitive adhesive applied over all or a portion of the bottom side of the composite to attach the drug delivery device to the skin of the patient. The medication permeates through the matrix that forms the drug containing reservoir, the membrane, if any, and the pressure sensitive adhesive, if the latter is positioned between the drug containing reservoir and the skin. The exposed surface of the pressure sensitive adhesive is generally covered by a release liner that is removed and discarded when the device is used.
A number of patents disclose the general concept of transdermal drug delivery devices. Representative of these are U.S. Pat. No. 3,598,122 to Zaffaroni, and U.S. Pat. No. 4,615,699 to Gale et al. Those patents disclose the use of silicone gels and similar substances as matrix compositions. Also, the use of elastomers has been suggested by incorporation of the drug into a prepolymer gum stock which is subsequently vulcanized, or by mixing the drug into a prepolymer along with a catalyst which promotes curing of the prepolymer at low temperatures. See, for example U.S. Pat. No. 4,435,180 to Leeper. The disadvantage of such systems is that the cure is not complete at the time the drug is incorporated into the composition, and the drug may therefore be deleteriously affected by either the vulcanizing temperatures, the prepolymer, which may contain reactive components that react with certain drugs, or the curing agent which may interact with some drugs. In the case of the latter interactions the drug inhibits the curing reaction in some cases, while the curing agent affects the efficacy of the drug in other cases.
Matrices formed of silicone rubber such as those disclosed in the prior art also tend to be insufficiently permeable to provide the desired release rate of a medication in the case of medications which are of an ionic, hydrophilic, or oleophobic nature. Hydrophobic silicone polymers are not preferred in such applications because of the limited permeability of ionic or hydrophilic drugs through the polymers which are of a hydrophobic nature.
U.S. Pat. No. 4,686,137, which issued to Ward and Riffle on Aug. 11, 1987, discloses the use as an additive in base polymers of polyurethane urea-silicone block copolymers consisting essentially of a "hard" segment that is preferably a polyurethane formed from the reaction of diphenylmethane diisocyanate with a diol, and a "soft" segment having both hydrophilic and hyrophobic portions. The hydrophobic portion of the soft segment can be a polymeric tetraalkylene oxide, such as polytetramethylene oxide, a polydialkylsiloxane, or a mixture of these two polymers, and the preferred hydrophilic segment is polyethylene oxide. These copolymers are combined with a base polymer, such as a polyurethane, and a suitable solvent to form films suitable for use as wound dressings or semipermeable membranes and as coating compositions for textile materials. There is no disclosure, however, of thermoplastic low temperature softening copolymers containing a major weight percentage of silicone segments, which would be desirable as a matrix or reservoir for a drug delivery device.
An objective of this invention is to provide materials for matrices that enable the migration therethrough of a variety of medications and which can be melted or softened to the extent that a drug can be admixed therein at relatively low temperatures, i.e., about 45.degree. C. to 160.degree. C., which temperature is low enough to avoid thermal damage to the drug. The matrices of the present invention are thermoplastic materials which do not require the presence of curing agents, prepolymers, or catalysts. By elimination of the need of using such agents which might themselves alter the rate of drug delivery or present either health hazards in addition to possibly impairing the efficacy of the medication being administered, a number of problems encountered with the prior art are eliminated. Also an important advantage in the ability to employ commercially feasible assembly methods in manufacture of drug delivery devices is attained.